tbuckley/cabot-search huggingface dataset:
Tomato flu outbreak in India: Why is it an impending public health emergency?- A correspondence
Authors: Anushree Rai, Olivier Uwishema, Aderinto Nicholas, Mortada Abbass, Lama Uweis, Sara Arab, Rayyan El Saleh, Irem Adanur, Daniel Stephen Masunga, Abubakar Nazir
Journal: International Journal of Surgery (2023)

Rai, Anushree; Uwishema, Olivier; Nicholas, Aderinto; Abbass, Mortada; Uweis, Lama; Arab, Sara; El Saleh, Rayyan; Adanur, Irem; Stephen Masunga, Daniel; Nazir, Abubakar Author Information
A novel NEDD4L-TXNIP-CHOP axis in the pathogenesis of nonalcoholic steatohepatitis
Authors: Qian Guo, Mingyang Xin, Qingchun Lu, Dechun Feng, Vicky Yang, Lee F. Peng, Kelly A. Whelan, Wenhui Hu, Sheng Wu, Xiaofeng Yang, Hong Wang, Brad S. Rothberg, Ana M. Gamero, Glenn S. Gerhard, Bin Gao, Ling Yang
Journal: Theranostics (2023)

Background: Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver diseases worldwide.There is a pressing clinical need to identify potential therapeutic targets for NASH treatment.Thioredoxin interacting protein (Txnip) is a stress responsive gene that has been implicated in the pathogenesis of NASH, but its exact role is not fully understood.Here, we investigated the liver-and gene-specific role of Txnip and its upstream/downstream signaling in the pathogenesis of NASH.Methods and Results: Using four independent NASH mouse models, we found that TXNIP protein abnormally accumulated in NASH mouse livers.A decrease in E3 ubiquitin ligase NEDD4L resulted in impaired TXNIP ubiquitination and its accumulation in the liver.TXNIP protein levels were positively correlated with that of CHOP, a major regulator of ER stress-mediated apoptosis, in NASH mouse liver.Moreover, gain-and loss-of-function studies showed that TXNIP increased protein not mRNA levels of Chop both in vitro and in vivo.Mechanistically, the C-terminus of TXNIP associated with the N-terminus of the α-helix domain of CHOP and decreased CHOP ubiquitination, thus increasing the stability of CHOP protein.Lastly, selective knockdown of Txnip by adenovirus-mediated shRNA (not targets Txnip antisense lncRNA) delivery in the livers of both young and aged NASH mice suppressed the expression of CHOP and its downstream apoptotic pathway, and ameliorated NASH by reducing hepatic apoptosis, inflammation, and fibrosis.Conclusions: Our study revealed a pathogenic role of hepatic TXNIP in NASH and identified a novel NEDD4L-TXNIP-CHOP axis in the pathogenesis of NASH.
Membership in the Council of Teaching Hospitals and Health Systems Among Emergency Medicine Residency Program–Sponsoring Institutions, 2001-2020
Authors: Christopher L. Bennett, Krislyn M. Boggs, Cameron J. Gettel, Wendy W. Sun, Arjun K. Venkatesh, Carlos A. Camargo
Journal: JAMA Network Open (2023)

This cross-sectional study identifies US institutions sponsoring residency programs and examines whether Council of Teaching Hospitals and Health Systems membership is associated with institution characteristics.
CAGEE: Computational Analysis of Gene Expression Evolution
Authors: Jason Bertram, Ben Fulton, Jason P Tourigny, Yadira Peña-Garcia, Leonie C Moyle, Matthew W Hahn
Journal: Molecular Biology and Evolution (2023)

Abstract Despite the increasing abundance of whole transcriptome data, few methods are available to analyze global gene expression across phylogenies. Here, we present a new software package (Computational Analysis of Gene Expression Evolution [CAGEE]) for inferring patterns of increases and decreases in gene expression across a phylogenetic tree, as well as the rate at which these changes occur. In contrast to previous methods that treat each gene independently, CAGEE can calculate genome-wide rates of gene expression, along with ancestral states for each gene. The statistical approach developed here makes it possible to infer lineage-specific shifts in rates of evolution across the genome, in addition to possible differences in rates among multiple tissues sampled from the same species. We demonstrate the accuracy and robustness of our method on simulated data and apply it to a data set of ovule gene expression collected from multiple self-compatible and self-incompatible species in the genus Solanum to test hypotheses about the evolutionary forces acting during mating system shifts. These comparisons allow us to highlight the power of CAGEE, demonstrating its utility for use in any empirical system and for the analysis of most morphological traits. Our software is available at https://github.com/hahnlab/CAGEE/.
Lactate-mediated Fascin protrusions promote cell adhesion and migration in cervical cancer
Authors: Xiao Han, Shujuan Du, Xiaoting Chen, Xuehua Min, Zhongwei Dong, Yuyan Wang, Caixia Zhu, Fang Wei, Shujun Gao, Qiliang Cai
Journal: Theranostics (2023)

Background: Lactate is associated with the poor prognosis of many human malignancies. Cervical cancer, one of main causes of women mortality worldwide, is aggressive and absent of effective pharmacological treatment, and its underlying mechanisms of progression remain elusive. Methods: The regulation of β-catenin to fascin protrusion formation upon acidic lactate (Lactic acid [LA]) stimulation was evaluated through in β-catenin or fascin deficiency cell line models by immunofluorescence assays, and subcellular fractionation. The effect of β-catenin and fascin relocation by LA and its antagonist were evaluated by immunohistochemistry assay in patient tissues and mouse tumor xenograft model. Trypsin digestion, Transwell assay, cell proliferation in vitro was performed to explore the role of LA in the cell growth, adhesion and migration. Results: Low concentration of LA significantly promotes cytoskeleton remodeling via `protrusion formation to increase cell adhesion and migration. Mechanistically, upon LA stimulation, β-catenin diffuses from the cytoplasmic membrane into the nucleus, which in turn induces fascin nuclear-cytoplasm redistribution to the protrusion compartment. Moreover, the antagonist of LA sufficiently blocks the LA-mediated β-catenin nuclear import, fascin nuclear export, and the growth and invasion of cervical cancer cells in vitro and in vivo using a murine xenograft model. Conclusions: This study uncovers β-catenin-fascin axis as a key signal in response to extracellular lactate and indicates that antagonist of LA may serve as a potential clinical intervention for cancer development.
A starch-based implant as a controlled drug release system: Non-invasive in vivo characterization using multispectral fluorescence imaging.
Authors: Golbarg Esfahani, Henrike Lucas, Frank Syrowatka, Karsten Mäder
Journal: Journal of Controlled Release (2023)

Solid implants are parenteral depot systems that can provide a controlled release of drugs in the desired body area over a few days to months. Finding an alternative for the two most commonly used polymers in the production of parenteral depot systems, namely Poly-(lactic acid) (PLA) and Poly-(lactide-co-glycolide) (PLGA), is of great importance due to their certain drawbacks. Our previous study showed the general suitability of starch-based implants for controlled drug release system. In this study, the system is further characterized and the release kinetics are investigated in vitro and in vivo by fluorescence imaging (FI). ICG and DiR, two fluorescent dyes with different hydrophobicity serving as a model for hydrophilic and hydrophobic drugs, have been used. In addition to 2D FI, 3D reconstructions of the starch implant were also used to assess the release kinetics in 3D mode. The in vitro and in vivo studies showed a fast release of ICG and a sustained release of DiR over 30 days from the starch-based implant. No treatment-related adverse effects were observed in mice. Our results indicate the promising potential of the biodegradable biocompatible starch-based implant for the controlled release of hydrophobic drugs.
Error in Byline
Journal: JAMA Network Open (2023)

Anda Bularga, MD; Caelan Taggart, MD; Filip Mendusic, MSc; Dorien M. Kimenai, PhD; Ryan Wereski, MD; Matthew T. H. Lowry, MD; Kuan Ken Lee, MD; Amy V. Ferry, PhD; Stacey S. Stewart, BSc; David A. McAllister, MD, PhD; Anoop S. V. Shah, MD, PhD; Atul Anand, MD, PhD; David E. Newby, MD, PhD; Nicholas L. Mills, MD, PhD; Andrew R. Chapman, MD, PhD; High-Sensitivity Troponin in the Evaluation of Patients with Suspected Acute Coronary Syndrome (High-STEACS) Investigators; Fiona E Strachan ; Christopher Tuck; Dimitrios Doudesis; Dennis Sandeman; Philip D Adamson; Jack P M Andrews; Alastair Moss; Mohamed S Anwar; John Hung; Catherine L Stables; Catalina A Vallejo; Athanasios Tsanas; Lucy Marshal; Takeshi Fujisawa; Mischa Hautvast; Jean McPherson; Lynn McKinley; Keith A A Fox; Colin Berry; Simon Walker; Christopher Weir; Ian Ford; Alasdair Gray; Paul O Collinson; Fred S Apple; Alan Reid; Anne Cruikshank; Iain Findlay; Shannon Amoils; Donogh Maguire; Jennifer Stevens; John Norrie; Jonathan Malo; Colin M Fischbacher; Bernard L Croal; Stephen J Leslie; Catriona Keerie; Richard A Parker; Allan Walker; Ronnie Harkess; Tony Wackett; Roma Armstrong; Marion Flood; Laura Stirling; Claire MacDonald; Imran Sadat; Frank Finlay; Heather Charles; Pamela Linksted; Stephen Young; Bill Alexander; Chris Duncan
Workplace Psychosocial Resources and Risk of Sleep Disturbances Among Employees
Authors: Tianwei Xu, Reiner Rugulies, Jussi Vahtera, Sari Stenholm, Jaana Pentti, Linda L. Magnusson Hanson, Göran Kecklund, Jimmi Mathisen, Mads Nordentoft, Mika Kivimäki, Naja Hulvej Rod
Journal: JAMA Network Open (2023)

Importance Workplace psychosocial resources naturally tend to cluster in some work teams. To inform work-related sleep health promotion interventions, it is important to determine the associations between clustering of workplace resources and sleep disturbances when some resources are high while others are low and to mimic an actual intervention using observational data. Objective To examine whether clustering of and changes in workplace psychosocial resources are associated with sleep disturbances among workers. Design, Setting, and Participants This population-based cohort study used data from the Swedish Longitudinal Occupational Survey of Health (2012-2018), the Work Environment and Health in Denmark study (2012-2018), and the Finnish Public Sector Study (2008-2014), collected biennially. Statistical analysis was conducted from November 2020 to June 2022. Exposure Questionnaires were distributed measuring leadership quality and procedural justice (ie, vertical resources) as well as collaboration culture and coworker support (ie, horizontal resources). Resources were divided into clusters of general low, intermediate vertical and low horizontal, low vertical and high horizontal, intermediate vertical and high horizontal, and general high. Main Outcomes and Measures Odds ratios (ORs) and 95% CIs were reported from logistic regression models for the associations between the clustering of resources and concurrent and long-term sleep disturbances. Sleep disturbances were measured by self-administered questionnaires. Results The study identified 114 971 participants with 219 982 participant-observations (151 021 [69%] women; mean [SD] age, 48 [10] years). Compared with participants with general low resources, other groups showed a lower prevalence of sleep disturbances, with the lowest observed in the general high group concurrently (OR, 0.38; 95% CI, 0.37-0.40) and longitudinally after 6 years (OR, 0.52; 95% CI, 0.48-0.57). Approximately half of the participants (27 167 participants [53%]) experienced changes in resource clusters within 2 years. Improvements in vertical or horizontal dimensions were associated with reduced odds of persistent sleep disturbances, and the lowest odds of sleep disturbances was found in the group with improvements in both vertical and horizontal dimensions (OR, 0.53; 95% CI, 0.46-0.62). A corresponding dose-response association with sleep disturbances was observed for decline in resources (eg, decline in both dimensions: OR, 1.74; 95% CI, 1.54-1.97). Conclusions and Relevance In this cohort study of workplace psychosocial resources and sleep disturbances, clustering of favorable resources was associated with a lower risk of sleep disturbances.
Inequalities in Exposure to Firearm Violence by Race, Sex, and Birth Cohort From Childhood to Age 40 Years, 1995-2021
Authors: Charles C. Lanfear, Rebecca Bucci, David S. Kirk, Robert J. Sampson
Journal: JAMA Network Open (2023)

The past quarter-century has seen both sharp declines and increases in firearm violence in the United States. Yet, little is known about the age of first exposure to firearm violence and how it may differ by race, sex, and cohort.To examine race, sex, and cohort differences in exposure to firearm violence in a representative longitudinal study of children who grew up in periods with varying rates of firearm violence in the United States and to examine spatial proximity to firearm violence in adulthood.This population-based representative cohort study included multiple cohorts of children followed-up from 1995 through 2021 in the Project on Human Development in Chicago Neighborhoods (PHDCN). Participants included Black, Hispanic, and White respondents from 4 age cohorts of Chicago, Illinois, residents, with modal birth years of 1981, 1984, 1987, and 1996. Data analyses were conducted from May 2022 to March 2023.Firearm violence exposure, including age when first shot, age when first saw someone shot, and past-year frequency of fatal and nonfatal shootings within 250 m of residence.There were 2418 participants in wave 1 (in the mid-1990s), and they were evenly split by sex, with 1209 males (50.00%) and 1209 females (50.00%). There were 890 Black respondents, 1146 Hispanic respondents, and 382 White respondents. Male respondents were much more likely than female respondents to have been shot (adjusted hazard ratio [aHR], 4.23; 95% CI, 2.28-7.84), but only moderately more likely to have seen someone shot (aHR, 1.48; 95% CI, 1.27-1.72). Compared with White individuals, Black individuals experienced higher rates of all 3 forms of exposure (been shot: aHR, 3.05; 95% CI, 1.22-7.60; seen someone shot: aHR, 4.69; 95% CI, 3.41-6.46; nearby shootings: adjusted incidence rate ratio [aIRR], 12.40; 95% CI, 6.88-22.35), and Hispanic respondents experienced higher rates of 2 forms of violence exposure (seen someone shot: aHR, 2.59; 95% CI, 1.85-3.62; nearby shootings: aIRR, 3.77; 95% CI, 2.08-6.84). Respondents born in the mid-1990s who grew up amidst large declines in homicide but reached adulthood during city and national spikes in firearm violence in 2016 were less likely to have seen someone shot than those born in the early 1980s who grew up during the peak of homicide in the early 1990s (aHR, 0.49; 95% CI, 0.35-0.69). However, the likelihood of having been shot did not significantly differ between these cohorts (aHR, 0.81; 95% CI, 0.40-1.63).In this longitudinal multicohort study of exposure to firearm violence, there were stark differences by race and sex, yet the extent of exposure to violence was not simply the product of these characteristics. These findings on cohort differences suggest changing societal conditions were key factors associated with whether and at what life stage individuals from all race and sex groups were exposed to firearm violence.
Phase I Study of SYNB1891, an Engineered <i>E. coli</i> Nissle Strain Expressing STING Agonist, with and without Atezolizumab in Advanced Malignancies
Authors: Jason J. Luke, Sarina A. Piha-Paul, Theresa Medina, Claire F. Verschraegen, Mary Varterasian, Aoife M. Brennan, Richard J. Riese, Anna Sokolovska, James Strauss, David L. Hava, Filip Janku
Journal: Clinical Cancer Research (2023)

Abstract Purpose: SYNB1891 is a live, modified strain of the probiotic Escherichia coli Nissle 1917 (EcN) engineered to produce cyclic dinucleotides under hypoxia, leading to STimulator of INterferon Genes (STING) activation in phagocytic antigen-presenting cells in tumors and activating complementary innate immune pathways. Patients and Methods: This first-in-human study (NCT04167137) enrolled participants with refractory advanced cancers to receive repeat intratumoral injections of SYNB1891 either alone or in combination with atezolizumab, with the primary objective of evaluating the safety and tolerability of both regimens. Results: Twenty-four participants received monotherapy across six cohorts, and 8 participants received combination therapy in two cohorts. Five cytokine release syndrome events occurred with monotherapy, including one that met the criteria for dose-limiting toxicity at the highest dose; no other SYNB1891-related serious adverse events occurred, and no SYNB1891-related infections were observed. SYNB1891 was not detected in the blood at 6 or 24 hours after the first intratumoral dose or in tumor tissue 7 days following the first dose. Treatment with SYNB1891 resulted in activation of the STING pathway and target engagement as assessed by upregulation of IFN-stimulated genes, chemokines/cytokines, and T-cell response genes in core biopsies obtained predose and 7 days following the third weekly dose. In addition, a dose-related increase in serum cytokines was observed, as well as stable disease in 4 participants refractory to prior PD-1/L1 antibodies. Conclusions: Repeat intratumoral injection of SYNB1891 as monotherapy and in combination with atezolizumab was safe and well tolerated, and evidence of STING pathway target engagement was observed.
Returning Individual Research Results from Digital Phenotyping in Psychiatry
Authors: Francis X. Shen, Matthew L. Baum, Nicole Martinez-Martin, Adam S. Miner, Melissa Abraham, Catherine A. Brownstein, Nathan Cortez, Barbara J. Evans, Laura T. Germine, David C. Glahn, Christine Grady, Ingrid A. Holm, Elisa A. Hurley, Sara Kimble, Gabriel Lázaro-Muñoz, Kimberlyn Leary, Mason Marks, Patrick J. Monette, Jukka-Pekka Onnela, P. Pearl O’Rourke, Scott L. Rauch, Carmel Shachar, Srijan Sen, Ipsit Vahia, Jason L. Vassy, Justin T. Baker, Barbara E. Bierer, Benjamin C. Silverman
Journal: The American Journal of Bioethics (2023)

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants' locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant's real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas.
Changes in Triglyceride Levels and Risk for Coronary Heart Disease in Young Men
Authors: Amir Tirosh, Assaf Rudich, Tzippora Shochat, Dorit Tekes-Manova, Eran Israeli, Yaakov Henkin, Ilan Kochba, Iris Shai
Journal: Annals of Internal Medicine (2007)

Background: Current triglyceride levels might be only a weak predictor of risk for coronary heart disease (CHD). Objective: To assess the association between changes over time in fasting triglyceride levels and CHD risk in young adults. Design: Follow-up study over 5.5 years after 2 measurements of fasting triglycerides 5 years apart. Setting: The Staff Periodic Examination Center of the Israel Defense Forces, Zrifin, Israel. Patients: 13 953 apparently healthy, untreated, young men (age 26 to 45 years) with triglyceride levels less than 3.39 mmol/L (<300 mg/dL). Measurements: Two triglyceride measurements (at enrollment [time 1] and 5 years later [time 2]), lifestyle variables, and incident cases of angiography-proven CHD. Results: Within 5.5 years, 158 new cases of CHD were identified. The multivariate model was adjusted for age; family history; fasting glucose; high-density lipoprotein cholesterol; blood pressure; body mass index; and changes between time 1 and time 2 in body mass index, physical activity, smoking status, and habit of eating breakfast. Investigators categorized triglyceride levels according to low, intermediate, and high tertiles (as measured at time 1 and time 2 [expressed as tertile at time 1/tertile at time 2]). The risk for CHD in men with high-tertile triglyceride levels at time 1 changed depending on the tertile at time 2 (hazard ratios, 8.23 [95% CI, 2.50 to 27.13] for high/high, 6.84 [CI, 1.95 to 23.98] for high/intermediate, and 4.90 [CI, 1.01 to 24.55] for high/low, compared with the stable low/low group). The risk for CHD in men with low-tertile levels at time 1 also changed depending on the tertile at time 2 (hazard ratios, 3.81 [CI, 0.96 to 15.31] for low/intermediate and 6.76 [CI, 1.34 to 33.92] for low/high, compared with the stable low/low group). Limitations: Participants were healthy and had a low incidence rate of CHD. The study was observational. Conclusions: Two triglyceride measurements obtained 5 years apart may assist in assessing CHD risk in young men. A decrease in initially elevated triglyceride levels is associated with a decrease in CHD risk compared with stable high triglyceride levels. However, this risk remains higher than in those with persistently low triglyceride levels.
Growth Factors and Wound Healing: Platelet-Derived Growth Factor as a Model Cytokine
Authors: Thomas F. Deuel, Rodney S. Kawahara, Thomas A. Mustoe, Glenn F. Pierce
Journal: Annual Review of Medicine (1991)

Cytokines such as the platelet-derived growth factor (PDGF) have the potential to initiate and mediate many if not all of the complex biological responses associated with inflammation and wound healing. PDGF is a potent cytokine that may be used to illustrate the diverse activities initiated by the interactions of PDGF with its receptor relevant to the inflammatory response and subsequent wound repair. Because PDGF can chemotactically attract, activate, and initiate new expression of quiescent genes (e.g. the small inducible gene, SIG, family), it fulfills the predictions anticipated of a candidate wound hormone. PDGF added directly to experimental wounds in animals enhances wound healing, which suggests that cytokines will become increasingly important as therapeutic agents in the treatment of wounds in humans.
Defining, Estimating, and Communicating Overdiagnosis in Cancer Screening
Authors: Louise Davies, Diana B. Petitti, Lynn Martin, Meghan Woo, Jennifer S. Lin
Journal: Annals of Internal Medicine (2018)

The toll of inadequate health care is well-substantiated, but recognition is mounting that "too much" is also possible. Overdiagnosis represents one harm of too much medicine, but the concept can be confusing: It is often conflated with related harms (such as overtreatment, misclassification, false-positive results, and overdetection) and is difficult to measure because it cannot be directly observed. Because the U.S. Preventive Services Task Force (USPSTF) issues screening recommendations aimed largely at healthy persons, it has a particular interest in understanding harms related to screening, especially but not limited to overdiagnosis. In support of the USPSTF, the authors summarize the knowledge and provide guidance on defining, estimating, and communicating overdiagnosis in cancer screening. To improve consistency, thinking, and reporting about overdiagnosis, they suggest a specific definition. The authors articulate how variation in estimates of overdiagnosis can arise, identify approaches to estimating overdiagnosis, and describe best practices for communicating the potential for harm due to overdiagnosis.